Quinazolin-4(3H)-one-type piperidine compounds and uses thereof

Abstract

The present disclosure relates to Quinazolin-4(3H)-one-Type Piperidine Compounds, such as those of Formule (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R 1 , R 2 , R 3 , Q, Y 1 , Z, A, B, E, and a are as defined herein; compositions comprising an effective amount of a Quinazolin-4(3H)-one-Type Piperidine Compound, and methods to treat or prevent a condition, such as pain, comprising administering to an animal in need thereof an effective amount of a Quinazolin-4(3H)-one-Type Piperidine Compound.

The invention claimed is: 
     
       1. A compound of Formula (Ia′): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof,
 wherein 
 A and B together form a (C 2 -C 6 )bridge, wherein the 6-membered, nitrogen-containing ring that is fused to the benzene ring is in the endo- or exo-configuration with respect to the A-B bridge; 
 R 3  is H, —(CH 2 ) d C(═Y)YT, or —(CH 2 ) d C(═Y)N(T) 2 , 
 Y, each independently, is O or S; 
 Z is a direct bond; 
 R 1  is —(C 3 -C 14 )cycloalkyl or —(C 6 -C 14 )bicycloalkyl, each of which is unsubstituted or substituted with R 5 ; 
 each T is independently selected from
 —H, or —(C 1 -C 10 )alkyl, unsubstituted or substituted with 1, or 2 independently selected R 5  groups 
 
 each R 5  is independently —(C 1 -C 6 )alkyl; 
 each R 7  is independently —H, or —(C 1 -C 6 )alkyl; 
 each d is an integer independently selected from 0, 1, 2, 3, 4, 5, and 6. 
 
     
     
       2. The compound of  claim 1 , wherein R 3  is —(CH 2 ) d C(═Y)YT or —(CH 2 ) d C(═Y)N(T) 2 . 
     
     
       3. The compound of  claim 1 , wherein R 3    
       is —(CH 2 ) d C(═Y)YT, wherein Y is O for each occurrence and d is 1 or 2, and T is —H or unsubstituted —(C 1 -C 6 )alkyl. 
     
     
       4. The compound of  claim 1 , wherein R 3  is —(CH 2 ) d C(═Y)N(T) 2 , wherein Y is O, d is 1 or 2. 
     
     
       5. The compound of  claim 4 , wherein one T is —H, and the other occurrence of T is —(C 1 -C 6 )alkyl substituted with at least one R 5 . 
     
     
       6. The compound of  claim 5 , wherein at least one R 5  in an occurrence of T of R 3  is —C(═O)OR 7 . 
     
     
       7. The compound of  claim 1 , wherein R 3  is —H. 
     
     
       8. The compound of  claim 1 , wherein A and B together form a bridge such that the bridged-piperidine is: 
       
         
           
           
               
               
           
         
       
       wherein the piperidine nitrogen is optionally in pharmaceutically acceptable salt form. 
     
     
       9. The compound of  claim 8 , wherein the 6-membered, nitrogen-containing ring that is fused to the benzene ring is in the endo-configuration with respect to the A-B bridge. 
     
     
       10. The compound of  claim 1 , wherein R 1  is —(C 6 -C 14 )bicycloalkyl, which is unsubstituted or substituted with R 5  wherein R 5  is —OR 7  or ═O. 
     
     
       11. The compound of  claim 1 , wherein —Z—R 1  is: 
       
         
           
           
               
               
           
         
       
     
     
       12. The compound of  claim 1 , wherein —Z—R 1  is: 
       
         
           
           
               
               
           
         
       
       R z  is —H or —(C 1 -C 6 )alkyl. 
     
     
       13. A compound selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and the pharmaceutically acceptable salts and solvates thereof. 
     
     
       14. The compound of  claim 13  selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and the pharmaceutically acceptable salts and solvates thereof. 
     
     
       15. A composition comprising an effective amount of the compound of  claim 1  and a pharmaceutically acceptable carrier or excipient. 
     
     
       16. A method for modulating ORL-1 receptor function in a cell, comprising contacting a cell capable of expressing the ORL-1 receptor with an effective amount of the compound of  claim 1 . 
     
     
       17. A method for treating pain in an animal, comprising administering to an animal in need thereof an effective amount of the compound of  claim 1 .